Method of making germinal gland hormone derivatives and product thereof



Patented Sept. 28, 1937 UNITED STATES PATENT OFFICE METHOD OF MAKINGGERMINAL GLAND HORMONE DERIVATIVES AND PRODUCT THEREOF Walter Schoeller,Berlin-Westend, Friedrich Hildebrandt, Hohen Neuendorf, near Berlin,Germany, and Erwin Schwenk, Bloomfield, N. J., assignors toSchering-Kahlbaum A. G., Berlin, Germany 7 v No Drawing. Originalapplication October 24,

1933, Serial No. 694,998. Divided and this application July 23, 1936,Serial No. 92,140. In Germany October 2'7, 1932 3 Claims.

wherein the substituent groups on each of the end rings are most likelyin the positions shown.

The present application is a division of our copending applicationSerial No. 694,998, filed October 24, 1933, and entitled Germinal glandhormone derivatives of the formula CmHzaOz and method of making same.

It is among the objects of this invention to treat the follicle hormonesin such a manner as to change the characteristics thereof and to provideproperties in derivatives so formed analogous to the properties of themale hormones.

It is further an object of this invention to provide a method wherebyderivatives of germinal gland hormones of the formula Ciel-12502 areobtained by using reduction products of follicle hormones as startingmaterials, said products having the following structural formula:

wherein the substituent groups on each of the end rings are most likelyin the positions shown, and subjecting the latter to first, an oxidizingtreatment and then a reducing treatment, whereby the desired product isobtained.

The reduction products of follicle hormones mentioned above include, forinstance, those products which are obtained by hydrogenating thefollicle hormones, such as the hormone of the formula Ciel-12202, andhaving most probably the following structural formula:

o The production of such compounds is described in our copendingapplication Serial No. 694,688, filed October 21, 1933, entitled Methodfor the production of hydrogenation products of the follicle hormones.

In practicing our invention, we may take the octahydrofollicle hormoneand subject the same to a sufficiently strong oxidation treatmentwhereby both of the secondary alcohol groups therein are oxidized toketone groups and thereafter subjecting the di-ketone so formed to areduction of such character that only one of the ketone groups istransformed into a secondary alcohol group, thus forming a ketoalcohol.

The derivatives of germinal gland hormones of the formula C18H28O2,obtained by the above described method, represent new hydroxyketones orketoalcohols which exhibit a very remarkable and beneficial effect uponthe growth of the capon comb. Thus, this invention enables one totransform the female germinal gland hormones into substances which arevery similar to the male germinal gland hormones and which have thedesired effects of the male hormones.

The following is an example illustrating the character of the presentinvention and giving a practical means of obtaining the desired result:

Example 1 gram of the reduction product of the follicle hormoneC18H30O2,

is oxidized at 60 C. by means of an excess of chromic acid and sulfuricacid. Thereby a diketone of the formula CisHzsOz is obtained, which hasmost probably the following structural formula:

wherein the substituent groups on each of the end rings is most probablyin the positions shown.

This product, without further purification, is dissolved in alcohol orglacial acetic acid, a platinum oxide catalyst is added to the solutionand hydrogen is passed through the latter until two atoms of hydrogenare absorbed. After filter-' ing off the catalyst, water is added to thefiltrate. Thereby a crystalline mass is precipitated which is purifiedby recrystallization from diluted alcohol. The ketoalcohol of theformula C1aH28O2 is obtained in white crystals.

Other oxidation agents may be used which are capable of oxidizing theoctahydrofollicle hormone CiaHsoOz which contains two secondary a1-cohol groups to the corresponding diketone Ciel-12602.

The reduction of the latter may be carried out not only by means ofcatalytically activated hydrogen, but also by means of hydrogenactivated in another manner, for instance, by atomic hydrogen orhydrogen in statu nascendi, or the like.

While we have described our invention giving a single specificembodiment thereof, it is, of course, understood that said example doesnot limit the invention but merely illustrates the same. It will beobvious to those skilled in the art that various changes may be made inthe details of operation, such as the temperatures, quantities ofmaterials used, types and characters of solvents, catalysts, and otherdetails. A different source of hydrogen for the reduction may be used aswell as a different means for the oxidation. The reactions involved neednot be carried to completion, whereby a mixture of products will result,but preferably the reactions are carried on as completely as practical.

These and other changes may be made in the details disclosed hereinwithout departing from the spirit of the invention, the scope of whichis defined in the claims appended hereto.

What we claim is:

1. A method of producing ketoalcohols of the formula 0181-12802 whichcomprises first subjecting reduction productsof the follicle hormones,having the following structural formula:

' OH; H-

wherein the substituent groups on each of the end rings are most likelyin the positions shown, to the action of oxidizing agents capable oftransforming alcohols into ketones so as to transform said reductionproducts into diketones having the following structural formula:

wherein the substituent groups on each of the end rings are most likelyin the positions shown, to the action of oxidizing agents capable oftransforming alcohols into ketones so as to transform said reductionproducts into diketones having the following structural formula:

and then partially hydrogenating said diketones to form ketoalcohols bysubjecting the same to activated hydrogen.

3. A product having the following structural formula:

wherein the substituent groups on each of the end rings are most likelyin the positions shown.

WALTER SCHOELLER. FRIEDRICH IHLDEBRANDT.

ERWIN SCHWENK.

